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Anxiety‑induced overactive bladder: The role of oxidative stress and NF‑κB signaling pathway with Hsp90 as a potential biomarker

  • Authors:
    • Zhipeng Zhou
    • Lina Xu
    • Han Wu
    • Huaishan Hong
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Provincial Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China, Department of Urology, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Anesthesiology, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian 350001, P.R. China
    Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 85
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    Published online on: January 12, 2026
       https://doi.org/10.3892/mmr.2026.13795
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Abstract

Overactive bladder (OAB) is a common condition that affects lower urinary tract symptoms and markedly affects the physical and mental health of individuals. While the cause of OAB is unclear, some studies suggest a possible link to psychological factors, particularly anxiety. Despite this, research on the connection between anxiety and OAB is limited. The present study aimed to explore anxiety‑induced OAB by analyzing clinical data and identifying key genes and pathways in vivo, ultimately providing new insights for diagnosing and treating OAB. Clinical data were analyzed to explore the relationship between anxiety and OAB. A chronic restraint stress model was used to induce anxiety, with histological scoring and cystometry assessing bladder function. Bladder transcriptomics identified key genes and pathways in OAB development. Differences in oxidative stress and NF‑κB pathway activity were validated using immunohistochemistry, enzyme‑linked immunosorbent assay and quantitative PCR. Clinical data showed a positive link between overactive bladder symptom scores and general anxiety disorder scale‑7, with higher urination urgency scores in OAB patients with anxiety. Analysis confirmed anxiety as an independent risk factor for OAB. In vivo experiments showed that anxiety induced OAB‑like symptoms in mice through oxidative stress and NF‑κB pathway activation, with RNA sequencing revealing key hub genes included heat shock protein 90 (Hsp90) aa1, Hsp90ab1 and Hsp90b1. The present study demonstrated that anxiety may precipitate the onset of OAB by activating oxidative stress and the NF‑κB signaling pathway. Hsp90 may serve as a potential biomarker for diagnosing anxiety‑induced OAB. Retrospectively registered on 1 April 2025, The present study received the identifier ChiCTR2500100548 from the Chinese Clinical Trial Registry.

View Figures

Figure 1

Flowchart of the present study. LUTS,
lower urinary tract symptoms; OAB, overactive bladder; CON,
control; OABSS, overactive bladder symptom scores; GAD-7,
generalized anxiety disorder scale-7.

Figure 2

Anxiety is an independent risk factor
for predicting OAB. (A) Correlation analysis between OABSS and
GAD-7. (B) Correlation analysis between urgency of urination and
GAD-7. (C) OABSS between OAB patients with and without anxiety. (D)
Urgency of urination between OAB patients with and without anxiety.
(E) Logistic regression model for predicting OAB based on anxiety.
(F) ROC curve analysis for the diagnostic performance of anxiety in
identifying OAB. Data were presented as Mean ± SD or median. T-test
or Mann-Whitney U-test was used to compare continuous
variables between two groups, Correlation analysis was performed
using Spearman's rank correlation coefficient, a stepwise
regression approach was applied to identify the most significant
predictors. The model's goodness-of-fit was assessed using the
Hosmer-Lemeshow test (*P<0.05, **P<0.01, ns, no statistical
difference). OAB, overactive bladder; OABSS, overactive bladder
symptom scores; GAD-7, generalized anxiety disorder scale-7; ROC,
receiver operating characteristic.

Figure 3

CRS induced anxiety-like behavior in
mice. (A) Flow chart of in vivo procedures. (B) Schematic
diagram of the behavioral experiment. (C) Display of OFT and EPMT
in CRS group and CON group mice. (D) The time spent in the central
area in the OFT. (E) The distance traveled in the central area in
the OFT. (F) The total distance traveled in the OFT. (G) Times into
the open arm in the EMPT. (H) Time spent in the open arm in the
EMPT. (I) Times into the closed arm in the EMPT. (J) Time spent in
the closed arm in the EMPT. Data were presented as mean ± SD (n=6).
P-values were calculated using a two-tailed unpaired Student's
t-test (**P<0.01, ***P<0.001, ns, no statistical difference).
CRS, chronic restraint stress; OFT, open field test; EPMT, elevated
plus maze test; CON, control.

Figure 4

Anxiety caused OAB-like symptoms in
mice. (A) Representative trace of cystometry urodynamic assay
during a 30 min continuous monitoring performed in the CON and CRS
group. Arrows indicate voiding contractions of the bladder, and
asterisks represent non-voiding contractions of the bladder. (B)
The number of bladder non-voiding contractions. (C) The number of
bladder voiding contractions. (D) Bladder peak pressure. (E)
Maximum bladder capacity. (F) H&E staining and histological
score of bladder tissues (scale bar, 1 mm). Data were presented as
the median with interquartile range. (G) Bladder weight/body weight
ratio. (H) Thickness of lamina propria of the bladder. (I)
Thickness of mucosal layer of the bladder. Data were presented as
mean ± SD. (n=6) P-values were calculated using a two-tailed
unpaired Student's t-test (*P<0.05, **P<0.01, ns, no
statistical difference). CRS, chronic restraint stress; CON,
control.

Figure 5

GO analysis for DEGs. (A) Biological
process for downregulated genes. (B) Molecular function for
downregulated genes. (C) Cellular component for downregulated
genes. (D) Biological process for upregulated genes. (E) Molecular
function for upregulated genes. (F) Cellular component for
upregulated genes. (n=3). The differential gene filtration
threshold was FDR <0.05, |log2FC|≥1.5. GO, Gene Ontology; DEGs,
differentially expressed genes.

Figure 6

KEGG pathway analysis for DEGs. (A)
KEGG pathway analysis for downregulated genes. (B) KEGG pathway
analysis for upregulated genes. (n=3). The differential gene
filtration threshold was FDR <0.05, |log2FC|≥1.5. KEGG, Kyoto
Encyclopedia of Genes and Genomes; DEGs, Differentially expressed
genes.

Figure 7

PPI network based on DEGs. The
selected hub genes were marked in red. (n=3). The differential gene
filtration threshold was FDR <0.05, |log2FC|≥1.5. PPI,
protein-protein interaction; DEGs, differentially expressed
genes.

Figure 8

Anxiety active oxidative stress and
NF-κB signaling. The concentration of (A) MDA, (B) GSH, (C) T-SOD,
(D) IL-6, (E) IL-1β and (F) TNF-α in the serum. The concentration
of (G) MDA, (H) GSH, (I) T-SOD, (J) IL-6, (K) IL-1β and (L) TNF-α
in the bladder. (M) Representative images of NF-κB in the bladder,
scale bar, 250 µm. (N) Average optical density of NF-κB in the
bladder. (O) Relative mRNA level of Nf-κb1 in the
bladder. (P) Representative immunohistochemistry of Hsp90aa1,
Hsp90ab1 and Hsp90b1 in the bladder, scale bar, 250 µm. (Q) The
average optical density analysis results of Hsp90aa1, Hsp90ab1 and
Hsp90b1 in the bladder. (R) Relative mRNA levels of Hsp90aa1
in bladder tissues. (S) Relative mRNA levels of Hsp90ab1 in
bladder tissues. (T) Relative mRNA levels of Hsp90b1 in
bladder tissues. Data were presented as the mean ± SD. n=3
in M, N, P and Q, n=6 in A-L, O and R-T for each group.
P-values were calculated using a two-tailed unpaired Student's
t-test (*P<0.05, **P<0.01, ***P<0.001). MDA,
malondialdehyde; GSH, glutathione; T-SOD, total superoxide
dismutase.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou Z, Xu L, Wu H and Hong H: <p>Anxiety‑induced overactive bladder: The role of oxidative stress and NF‑&kappa;B signaling pathway with Hsp90 as a potential biomarker</p>. Mol Med Rep 33: 85, 2026.
APA
Zhou, Z., Xu, L., Wu, H., & Hong, H. (2026). <p>Anxiety‑induced overactive bladder: The role of oxidative stress and NF‑&kappa;B signaling pathway with Hsp90 as a potential biomarker</p>. Molecular Medicine Reports, 33, 85. https://doi.org/10.3892/mmr.2026.13795
MLA
Zhou, Z., Xu, L., Wu, H., Hong, H."<p>Anxiety‑induced overactive bladder: The role of oxidative stress and NF‑&kappa;B signaling pathway with Hsp90 as a potential biomarker</p>". Molecular Medicine Reports 33.3 (2026): 85.
Chicago
Zhou, Z., Xu, L., Wu, H., Hong, H."<p>Anxiety‑induced overactive bladder: The role of oxidative stress and NF‑&kappa;B signaling pathway with Hsp90 as a potential biomarker</p>". Molecular Medicine Reports 33, no. 3 (2026): 85. https://doi.org/10.3892/mmr.2026.13795
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou Z, Xu L, Wu H and Hong H: <p>Anxiety‑induced overactive bladder: The role of oxidative stress and NF‑&kappa;B signaling pathway with Hsp90 as a potential biomarker</p>. Mol Med Rep 33: 85, 2026.
APA
Zhou, Z., Xu, L., Wu, H., & Hong, H. (2026). <p>Anxiety‑induced overactive bladder: The role of oxidative stress and NF‑&kappa;B signaling pathway with Hsp90 as a potential biomarker</p>. Molecular Medicine Reports, 33, 85. https://doi.org/10.3892/mmr.2026.13795
MLA
Zhou, Z., Xu, L., Wu, H., Hong, H."<p>Anxiety‑induced overactive bladder: The role of oxidative stress and NF‑&kappa;B signaling pathway with Hsp90 as a potential biomarker</p>". Molecular Medicine Reports 33.3 (2026): 85.
Chicago
Zhou, Z., Xu, L., Wu, H., Hong, H."<p>Anxiety‑induced overactive bladder: The role of oxidative stress and NF‑&kappa;B signaling pathway with Hsp90 as a potential biomarker</p>". Molecular Medicine Reports 33, no. 3 (2026): 85. https://doi.org/10.3892/mmr.2026.13795
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